Alpine Research Labs
    Completed Preclinical (in vitro) 2007

    An analog of thyrotropin-releasing hormone (TRH) is neuroprotective against glutamate-induced toxicity in fetal rat hippocampal neurons in vitro

    Veronesi MC, Yard M, Jackson J, et al.

    Brain Research

    DOI: 10.1016/j.brainres.2006.10.029

    PE-22-28

    Summary

    Showed that a TRH analog (3-Methyl-Histidine TRH) protected fetal hippocampal neurons against glutamate-induced excitotoxicity in a concentration-dependent manner. Provides evidence for TRH analogs as neuroprotective agents in conditions involving glutamate toxicity.

    Key Findings

    • TRH analog protected hippocampal neurons from glutamate excitotoxicity in dose-dependent manner
    • Prolonged exposure to the TRH analog alone showed no cytotoxicity
    • Supports therapeutic potential of TRH analogs in neurodegenerative diseases involving excitotoxicity

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    Completed 2015

    First-in-class thyrotropin-releasing hormone (TRH)-based compound binds to a pharmacologically distinct TRH receptor subtype in human brain and is effective in neurodegenerative models

    Kelly JA, Boyle NT, Cole N, et al.

    Neuropharmacology

    Demonstrated that a TRH-based compound selectively binds a novel TRH receptor subtype in human hippocampus distinct from pituitary TRH receptors. Showed significant neuroprotective effects in kainate-induced neurodegeneration, free radical damage, and ALS mouse models while crossing the blood-brain barrier.

    • Identified a pharmacologically distinct TRH receptor subtype in human hippocampus
    • Reduced cognitive deficits in kainate-induced neurodegeneration model
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    DOI: 10.1016/j.neuropharm.2014.09.024

    Completed 1999

    Novel TRH analog improves motor and cognitive recovery after traumatic brain injury in rodents

    Faden AI, Fox GB, Fan L, et al.

    American Journal of Physiology

    Developed a dual-substituted TRH analog (2-ARA-53a) that preserved neuroprotective activity while eliminating undesirable autonomic, analeptic, and endocrine effects. Treatment improved both motor recovery and cognitive water maze performance after traumatic brain injury in rodents.

    • TRH analog improved motor recovery in rats and cognitive performance in mice after TBI
    • Successfully dissociated neuroprotective effects from endocrine and autonomic side effects
    pe-22-28

    DOI: 10.1152/ajpregu.1999.277.4.R1196